Monday 14 October 2013 – 3am PST
When US scientists gave non-exercising mice a protein produced by exercising mice, they found it switched on genes that help preserve brain health and boost growth of new nerves in regions important for learning and memory.

They suggest their findings could pave the way to a drug that improves treatments against cognitive decline in older people and help slow progression of brain-wasting diseases like Alzheimer’s and Parkinson’s.

Dr. Bruce Spiegelman, from Dana-Farber Cancer Institute and Harvard Medical School in Boston reports the discovery in the latest online issue of the journal Cell Metabolism.

Endurance exercise has previously been shown to improve brain function, particularly in older people. But until this study the underlying molecular mechanisms were not understood.

In an earlier study, Dr. Spiegelman’s team had already discovered that the protein, called FNDC5, is released into the bloodstream as a variant called irisin as a result of muscular exertion.

In this latest work, the researchers monitored the effect of endurance exercise on mice (they voluntarily ran on an exercise wheel for 30 days).

Boosting production of FNDC5

They found endurance exercise increased the effect of a regulatory metabolic compound, PGC-1alpha in the muscles of mice, which boosted production of FNDC5. This had the knock-on effect of switching on genes that increased the expression of a brain-protective protein, BDNF, in the hippocampus, a part of the brain involved in learning and memory.

Researchers found that a protein produced during exercise switches on genes that preserve brain health.

The hippocampus is only one of two areas in the adult brain that can grow new nerve cells. Exercise increases the effect of BDNF in the hippocampus, where it preserves brain cells and promotes the growth of new nerves and synapses or junctions between nerve cells, thereby aiding learning and memory.

But until now it was not clear what linked exercise to BDNF at the molecular level, which is what you need to know in order to develop drugs that have the same effect.

This study is the first to suggest that the molecular pathway that links exercise to raised BDNF activity goes via PGC-1alpha and FNDC5.

However, the authors suggest there may also be other pathways, waiting to be discovered.

In a second stage of the study, the researchers showed artificially increasing FNDC5 without the help of exercise had the same effect.

Dr. Spiegelman says:

“What is exciting is that a natural substance can be given in the bloodstream that can mimic some of the effects of endurance exercise on the brain.”

However, he cautions that more studies are now needed to find out whether giving mice FNDC5 actually leads to improved brain function.

Also, the researchers did not establish whether it was FNDC5 itself that ended up in the brains of the mice, or its variant, irisin.

If drug developers choose to start with irisin, they will first have to make a more stable form of the protein, says Dr. Spiegelman.

Funds from the JPB Foundation and National Institutes of Health helped finance the study.

Earlier this year, researchers from Princeton University reported in the Journal of Neuroscience that physicalexercise helps the brain withstand stress.

Written by Catharine Paddock PhD


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